Comparison of fluconazole, amphotericin B and flucytosine in treatment of a murine model of disseminated infection with Candida glabrata in immunocompromised mice

Candida glabrata is an emerging opportunist pathogen in immunosuppressed patients. C. glabrata is resistant to many antifungal agents and until recently, there have been no standard treatment regimens for this organism. A mouse model was established using mice immunosuppressed with 5 fluorouracil to evaluate amphotericin B, flucytosine, fluconazole and their combinations to treat an intravenously induced C. glabrata infection. Treatment with fluconazole, flucytosine, amphotericin B or a combination was begun one day after infection. Following 5 days of treatment, the mice were killed for fungal counts in kidneys and spleen. At the doses used, amphotericin B was superior to fluconazole or flucytosine alone in the treatment of C. glabrata infections. Flucytosine reduced the fungal burden in the kidney for only two of four isolates of C. glabrata. The combination of fluconazole and flucytosine was superior to these agents alone in reducing the tissue burden in the kidney for one isolate of C. glabrata. High doses of fluconazole alone produced modest reductions in kidney counts but did not reduce spleen tissue counts. There was poor correlation between in-vitro MICs and in-vivo results.